Superactivation of p53 Using Drug Combinations and New Insights into p53 Functions and Anticancer Therapy
- 1Laboratory of Preclinical Models, Maria Skłodowska-Curie National Research Institute of Oncology, Gliwice Branch, 44-101 Gliwice, Poland
Abstract
The p53 tumour suppressor protein exerts its influence on cells by regulating the expression of more than one thousand genes. To study p53 functions, cells are treated with various p53 activators, mostly established or experimental anticancer drugs. Some of these substances strongly collaborate in the activation of p53, which is manifested by a pronounced increase in the number of p53 molecules phosphorylated at both the amino and carboxyl terminus, a sign of p53 activation. Another manifestation of this collaboration is an increase in the number of upregulated genes. A good example of apparent synergy is the treatment of cells with actinomycin D and nutlin-3a, although other drug combinations show similar effects. The molecular mechanism underlying this collaboration is not precisely known. This superactivation of p53 has potential therapeutic applications. For example, it strongly sensitises cancer cells to apoptosis induced by FASLG, a ligand of the FAS death receptor. Moreover, superactivated p53 enables the identification of new p53 target genes, which helps us to better understand poorly studied p53 functions, such as the regulation of innate immunity, modification of cell microenvironments, removal of apoptotic bodies, tissue repair, and hormone production. However, innovative drug combinations targeting the p53 pathway have yet to be successfully translated into clinical practice.
Related
- Novel Palladium(II) β-Diketonate Complexes: Synthesis, Dual Antimicrobial/Anticancer Activity, and Molecular Insights into DNA/Protein Interactions
- Lighting up cancer: latest discoveries in ruthenium(ii) polypyridyl complexes for anticancer photodynamic therapy.
- Effectiveness and safety of a New Standardised TrEatment Protocol based on initial/early therapy with single-pill combinations of blood pressure-lowering drugs for improving blood pressure control (NewSTeP): Rationale, design of a randomized clinical trial and baseline characteristics of the trial participants
- ABC transporter genetic polymorphisms in cancer therapy: implications for anticancer drug disposition, efficacy, and toxicity
- Efficacy and safety of thymosin combined with anticancer therapy for colorectal cancer: a systematic review and meta-analysis of controlled studies
BibTeX
@article{rusin2026superactivation,
title = {{Superactivation of p53 Using Drug Combinations and New Insights into p53 Functions and Anticancer Therapy}},
author = {Marek Rusin and Małgorzata Krześniak and Barbara Łasut-Szyszka},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27208964},
url = {https://www.mdpi.com/1422-0067/27/20/8964},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Superactivation of p53 Using Drug Combinations and New Insights into p53 Functions and Anticancer Therapy
AU - Marek Rusin
AU - Małgorzata Krześniak
AU - Barbara Łasut-Szyszka
PY - 2026
DA - 2026/10/09
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27208964
UR - https://www.mdpi.com/1422-0067/27/20/8964
AB - The p53 tumour suppressor protein exerts its influence on cells by regulating the expression of more than one thousand genes. To study p53 functions, cells are treated with various p53 activators, mostly established or experimental anticancer drugs. Some of these substances strongly collaborate in the activation of p53, which is manifested by a pronounced increase in the number of p53 molecules phosphorylated at both the amino and carboxyl terminus, a sign of p53 activation. Another manifestation of this collaboration is an increase in the number of upregulated genes. A good example of apparent synergy is the treatment of cells with actinomycin D and nutlin-3a, although other drug combinations show similar effects. The molecular mechanism underlying this collaboration is not precisely known. This superactivation of p53 has potential therapeutic applications. For example, it strongly sensitises cancer cells to apoptosis induced by FASLG, a ligand of the FAS death receptor. Moreover, superactivated p53 enables the identification of new p53 target genes, which helps us to better understand poorly studied p53 functions, such as the regulation of innate immunity, modification of cell microenvironments, removal of apoptotic bodies, tissue repair, and hormone production. However, innovative drug combinations targeting the p53 pathway have yet to be successfully translated into clinical practice.
SN - 1422-0067
ER -